Sample preparation devices and systems

ABSTRACT

Devices and system for preparing samples are described. Such devices can comprise fluidic chambers, reservoirs, and movable structures for controlling the movement of samples. The device can also comprise functional elements for performing specific operations.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application claims priority to U.S. Provisional ApplicationNo. 61/580,035, filed on Dec. 23, 2011, which is incorporated herein byreference in its entirety.

FIELD

The present disclosure relates to fluidic devices that can facilitatepreparation of samples. Moreover, it relates to sample preparationdevices and systems.

BACKGROUND

A variety of methods are available to prepare fluidic samples forperforming scientific experiments. However, some devices used forpreparing samples can be expensive, bulky, and can have large deadvolume space. Low cost, portable, reliable, and easy to use devices canbe desirable to overcome such problems. With improved sample preparationdevices, scientific analysis such as PCR, ELISA, orfluorescence/absorbance analysis can be perform more easily andaccurately.

SUMMARY

According to a first aspect, a device for performing fluidic operationsis described, the device comprising: a fluidic chamber having aplurality of pairs of ports, a first port of each pair being located ona first side of the fluidic chamber and a second port of each pair beinglocated on a second side of the fluidic chamber, each second port beingopposite a respective first port; a plurality of reservoirs adapted tobe fluidly connected with the fluidic chamber at each of the pluralityof pairs of ports, the plurality of reservoirs configured to flow fluidfrom a reservoir on the first side of the fluidic chamber to a reservoiron the second side of the fluidic chamber, or vice versa; and astructure slidably moveable within the fluidic chamber, the structurehaving one or more openings adapted to be aligned through sliding of thestructure with at least one pair of ports to allow fluidic connectionbetween one or more reservoirs on the first side and respective one ormore reservoirs on the second side, the one or more openings beingalignable with a desired pair of ports through said sliding.

According to a second aspect, a device for performing fluidic operationsis described, the device comprising: an adapter comprising at least onepair of ports; a plurality of reservoirs fluidly connectable with the atleast one pair of ports, the plurality of reservoirs configured to flowfluid from at least a first reservoir to at least a second reservoir;and a first structure associated with the adapter and displaceable withrespect to the adapter, the first structure comprising a first channelarrangement configured to fluidly connect the at least first reservoirwith the at least second reservoir, the first channel arrangement beingalignable with a desired pair of ports through displacement of the firststructure.

According to a third aspect, a device for performing fluidic operationsis described, the device comprising: a first fixed structure and asecond fixed structure having a plurality ports; a plurality ofreservoirs adapted to be fluidly connected with the plurality of ports,the plurality of reservoirs configured to flow fluid from a reservoirassociated with the port on the first fixed structure to a reservoirassociated with the port on the second fixed structure, or vice versa;and a structure slidably moveable between the first fixed structure andthe second fixed structure, the structure having one or more openingsadapted to be aligned through sliding of the structure with at least oneport of the first fixed structure and at least one port of the secondfixed structure to allow fluidic connection between one or morereservoirs associated with the first fixed structure and respective oneor more reservoirs associated with the second fixed structure, the oneor more openings being alignable with a desired pair of ports throughsaid sliding.

According to a fourth aspect, a method of performing fluidic operationsusing the device according to claim 2 is described, the methodcomprising: a) slidably moving the structure to align the at least oneopening with a first pair of ports; b) transferring the fluid from thereservoir on the first side of the fluidic chamber to the reservoir onthe second side of the fluidic chamber by flowing the fluid through thefunctional element in the opening; and c) repeating a)-b) a desirednumber of times.

BRIEF DESCRIPTION OF DRAWINGS

The accompanying drawings, which are incorporated into and constitute apart of this specification, illustrate one or more embodiments of thepresent disclosure and, together with the description of exampleembodiments, serve to explain the principles and implementations of thedisclosure.

FIGS. 1-7 show cross-sectional views of exemplary fluidic devices with astructure being slidably moveable in an axial direction.

FIGS. 8-9 show cross-sectional views of exemplary fluidic devices with astructure being slidably moveable in a radial direction.

FIGS. 10, 11, and 12A-12E show cross-sectional and perspective views offluidic devices with a displaceable structure.

FIG. 13 shows the displaceable structure with a fluidic channel and afunctional element.

FIG. 14 shows a second displaceable structure located above anotherdisplaceable structure.

FIG. 15 shows a perspective view of the displaceable structureassociated with an adapter.

FIG. 16 shows a close-up cross-sectional view of the displaceablestructure associated with the adapter.

FIG. 17 shows a cross-sectional view of a possible configuration of twofluidic channels in the displaceable structure.

FIGS. 18A-18D show cross-sectional and perspective views of fluidicdevices with a structure being slidably moveable in an axial direction.

DETAILED DESCRIPTION

Some embodiments of the present disclosure describe devices, systems andmethods for performing fluidic operations and fluidic routing. Samplescan be prepared for various diagnostic and analytical tests, fluidrouting, complex manifold replacement as well as other operations. Someembodiments can allow for manual and/or automated operation. Theinvention allows rapid and reliable operation. It is low cost andobviates many problems possessed by present design and systems.

In some embodiments, complex fluid routing and operations can beperformed without (or with fewer number of) valves and channels.Furthermore, dead volume space can be very low (or zero) for fluidmovement between fluids located at relatively long distances. Theinvention allows a universal way to perform very complex fluidicoperations with a much simpler design. A sequence of operation can beestablished on-the-fly depending on type of sample thus allowinguniversal sample processing units. It also allows mix and match and onthe fly reconfiguration and design, thus being a truly modular andcustomizable. It allows flexibility in sequence of operations dependingon sample type. It allows parallel operations in some cases allowingmultiple operations to run at the same time. The invention is useful forcartridge, lab on chip and other design approaches. The invention allowsscalable design and the devices on these concepts can be made of a largerange of dimensions. It also allows universal sample type inputcapability. Although we describe sample preparation for examples, theinvention is also useful for wide variety of applications includingfluid manipulation, chemical and biological analysis, food safety, drugtesting, fluid metering and many others.

FIG. 1 shows an exemplary device 100 for performing fluidic operations.In some embodiments, the device 100 can comprise a fluidic chamber 102having a plurality of ports 104 a/b-110 a/b. The ports can be configuredin pairs such that a respective port for a particular port is located onan opposite side of the fluidic chamber 102, as shown, for example, port104 a and a respective port 104 b, and so on.

In some embodiments, a plurality of reservoirs can be fluidly connected(e.g., luer connection) with the fluidic chamber 102 at one or more ofthe ports. Such configuration allows for flowing fluid from thereservoir to or through the fluidic chamber 100 to another reservoirconnected with an opposite side of the fluidic chamber 102 at anotherport. By way of example and not of limitation, reservoirs can besyringes, custom shaped syringes, tubes with or without pinchingmechanisms, planar reservoirs and channels with a chip, pouches,collapsible pouches, reagent storage, or cartridges. However, thoseskilled in the art would understand that other types of reservoirs canalso be utilized.

In some embodiments, a slidably moveable structure 114 can be locatedwithin the fluidic chamber 102. Such moveable structure 114 can have anopening 116 such that when the opening 116 is aligned with one or moreports (e.g., ports 106 a and 106 b), fluid is able to flow from onereservoir to another reservoir, through the opening.

In some embodiments, the opening 116 in the moveable structure 114 cancomprise a functional element 118. A functional element 118 can bedefined as a something that performs a particular function when thefluid flows through the opening 116. By way of example and not oflimitation, functional elements 118 can be one or more of a DNA bindingmatrix, lysis structure, plasma filter, cell filter, mixing filter,binding filter, washing element, mixing element, bacteria filter, virusfilter, cytometry, analysis element, de-bubbler, di-electrophoresis,impedance spectroscopy, fluorescence/absorbance measuring elements,clear channel, capillary filling, and/or droplet generation. Therefore,when the fluid flows through the opening 116, the fluid can have aninteraction with the functional element 118. In the case of the DNAbinding matrix, when a fluid containing DNA flows through the DNAbinding matrix, the DNA binds to the matrix, thus capturing the DNA.

In some embodiments, a fluidic pressuring mechanism 120 can beconfigured to facilitate movement of the fluid from the associatedreservoir to the fluidic chamber 102. Such fluidic pressuring mechanism120 can be, by way of example and not of limitation, pistons, actuators,pumps, or valves. Pistons can have various sizes and shapes, forexample, to function with a syringe. Actuators can be internal to thereservoir or external to the reservoir. Pumps can also be internal orexternal to the reservoir, and can be electrochemical pumps, parasiticpumps, electro-osmotic pumps or vacuum pumps. Electro-osmotic pumps canbe used to pump elute buffer with DNA in the cartridge. In someembodiments, a membrane can be used to press down in the reservoir, thusforcing the fluid to flow. The fluidic pressure obtained from suchfluidic pressuring mechanism can comprise positive or negative pressure.For example, the fluid can be pushed from the source of the fluid, orpulled from the destination of the fluid. However, those skilled in theart would understand that other types of pressuring mechanisms arepossible to facilitate the movement of the fluid.

FIGS. 2A-2D shows an exemplary fluidic procedure for obtaining DNA. Byway of example and not of limitation, a first reservoir 200 a on a firstside 210 of the fluidic chamber 208 can contain a fluidic sample such asa lysate mixture. The fluidic pressuring mechanism 214 can push thelysate mixture from the first reservoir 200 a on the first side 210 ofthe fluidic chamber 208 to a first reservoir 200 b on a second side 212of the fluidic chamber 208, through the opening 216 in the moveablestructure 220. As the fluid flow through the opening 216, the functionalelement 218 (e.g., DNA binding matrix) can capture the DNA and the fluidcan continue to flow through/past the functional element 218, to thesecond reservoir 200 b. Once the DNA is captured in the functionalelement 218, the moveable structure 220 can be moved to a secondposition as shown in FIG. 2B. In the configuration shown in FIG. 2B, themoveable structure 220 is slid to the right such that the opening 216 isnow aligned with a pair of second reservoirs 202 a/b. The secondreservoir 202 b on the first side 210 of the fluidic chamber 208 cancomprise a solution, by way of example and not of limitation, water towash the DNA that is captured in the functional element 218 (e.g., DNAbinding matrix). The fluidic pressuring mechanism 214 can be used againto push the water from the second reservoir 202 a on the first side 210of the fluidic chamber 208 to the second reservoir 202 b on the secondside 212 of the fluidic chamber 208. A process can be repeated as manytimes as desired as shown in FIG. 2C according to the fluidic operationbeing performed, which can be determined by those having ordinary skillin the art. Finally, in the exemplary embodiment shown in FIG. 2D, afourth reservoir 206 can comprise an elution buffer to elute the DNAfrom the functional element 218 (e.g., DNA binding matrix). A cartridgeor a pouch can be connected with the second side 212 of the fluidicchamber 208 to collect the DNA as a result of the elution. An externalultrasonic or vibration device can be coupled with the reservoir(internally or externally) to mix the fluid in the reservoir.

In some embodiments, the moveable structure 300 shown in FIG. 3 cancomprise more than one openings 302-305. Each of the openings cancomprise the same or different functional elements 306-308 according tothe desired fluidic operation to be performed. In some embodiments, theopening 305 does not necessarily comprise a functional element.Alternatively, the opening 305 can comprise a channel for routing thefluid from one reservoir to another reservoir. In some embodiments, thefluidic chamber can comprise more than one moveable structures, one ontop of another. Such moveable structures can slides in an axialdirection as shown or along a curved path. Therefore, more than oneapplication or operation can be performed simultaneously. Thetemperature of the fluidic device can be controlled to optimizefunctionality (e.g. bonding condition) of the functional element.

FIGS. 4A-4D show alternative configurations of the fluidic chamber andreservoirs. By way of example and not of limitation, FIG. 4A showscartridges 400-403 as reservoirs in addition to those shown in FIGS.1-3. Accordingly, the moveable structure 114 can be moved along an axialdirection of the device to perform the fluidic operation and ultimatelyfill the cartridges 400-403 with, for example, DNA from the functionalelement 118. Additionally, as shown in FIGS. 4C-4D, the pair or ports404 a/b-406 a/b are not necessarily located directly opposite to itsrespective port. Alternatively, the cartridges can be replaced withtubes or well plate. Examples of applications using the method shows inFIGS. 4A-4D can include, for example, but not be limited to separatingserum and plasma for ELISA or other immunoassay operations. Results canbe read using, for example, fluorescence or other methods known by thoseskilled in the art.

FIG. 5 shows an exemplary configuration of the fluidic device 500 whenused to perform, for example, sample preparation for Polymerase ChainReaction (PCR). The fluidic chamber 512 can comprise a plurality ofports 513 and have a moveable structure 501 configured to slide withinthe fluidic chamber 512. The moveable structure 501 can have a firstopening 502 with a functional element (e.g., DNA binding matrix) and asecond opening 505 without a functional element. The plurality ofreservoirs 504 (e.g., syringes) and the moveable structure 501 can beused to wash and elute the sample in a sequence as described in previousparagraphs. Cartridges 510, 511 can also be connected with the ports 513and the cartridges can be further connected with other devices such as ahybridization chamber 506 or capillary electrophoresis 507. The syringesused can be low cost syringes and the syringe can be direction appliedto the fluidic chamber 512. As a consequence of the moveable structure501, the fluidic chamber 512 can be valveless and channels having deadvolume can be minimized in the fluidic chamber 512. The amount of deadvolume space is unaffected by varying the size and/or relative distancesof the reservoir 504 and the moveable structure 501 since when themoveable structure 501 is aligned with the ports 513, the entire opening502 is part of the flow path of the fluid. When the moveable structure501 is moved to a new position, the same opening can be used at the flowpath, thereby almost completely eliminating any dead volume space.

In some embodiments, the syringes and the moveable structure 501 can beoperated manually by a user or the entire operation can be automated by,for example, motors configured to move the moveable structure 501,operate the syringes, and/or the hybridization chamber 506. In someembodiments, a motor with a screw can be used to drive the moveablestructure. For rotary design moveable structures, a stepper motor can beused. A single fluidic device can comprise both manual and automatedoperation so that in cases where power is unavailable (e.g., deadbattery, emergency), manual operation can be used. The entire fluidicdevice can be a closed system thus avoiding contamination issues.

In some embodiments, multiple lysis operations can be integrated in thereservoir and the moveable structure. For example, tough bacteria orgram positive bacteria can have beads. In such case, the sample can beplaced in a lysis reservoir. Alternatively, there can be beads insidethe moveable structure or the reservoir for bead beating. In someembodiments, cells greater than certain sizes can be retained to performlysis, which can be helpful in the case of Malaria. In some embodiments,different DNA and/or RNA can be obtained through different sequencesfrom the same sample from a person. Some embodiments allows foron-the-fly or field mix-and-match of modules for sample processing.

FIGS. 6-7 show alternative configurations of the fluidic device. Forexample, the reservoirs 601 in FIG. 6 is shown with springs 602 to causemovement of the fluid from the reservoir. FIG. 7 is shown with aflexible pouch 701 as reservoirs.

FIG. 8 shows an exemplary embodiment of a fluidic device 800 having amoveable structure 802 that can be configured to slide in a radialdirection of the device as shown with arrow 804. Similarly to theconfiguration of the fluidic devices shown in FIGS. 1-7, the fluidicdevice 800 in FIG. 8 has a plurality of ports 805 a/b-806 a/b andreservoirs 803. The moveable structure 802 can comprise one or moreopenings 807, which can be aligned with the plurality of ports such thatwhen the opening is aligned, by way of rotating the moveable structure802, the fluid can flow from the reservoir on a first side of thereservoir to a second side of the reservoir. Accordingly, the opening807 can comprise a functional element 808 such as a DNA binding matrix.

FIGS. 9A-9D show a fluidic process that can be equivalent to theexemplary fluidic procedure for obtaining DNA as shown in FIGS. 2A-2Dusing a moveable structure 802 that can rotate radially.

FIGS. 10-11 show another exemplary fluidic device 1000 for performingfluidic operations, similarly to the device described for FIGS. 1-9. Thedevice 1000 can comprise an adapter 1001 having at least one pair ofports 1002 a/b, and a plurality of reservoirs 1007, 1008 that can beconnectable with the ports. The device 1000 can also comprise astructure 1003 that can be displaceable with respect to the adapter1001. By way of example and not of limitation, the structure 1003 canrotate in radial direction as shown with an arrow 1004. The structurecan comprise a fluidic channel arrangement 1005 adapted to allow fluidto flow. The channel arrangement 1005 can be a single channel or aplurality of channels making up the channel arrangement 1005. Thechannel arrangement 1005 can comprise a functional element 1006 withinthe fluidic path of the channel arrangement 1005.

In some embodiments, the plurality of channels can be adapted to allowflow cytometry using fluorescence, absorbance, impedance or otherdetection mechanism. Hydrodynamic focusing can be achieved with a 3Ddesign of the plurality of channels in the displaceable structure. Highpressure can be applied by using a piston to speed up the operation ofthe fluidic device. To perform fluorescence, absorbance, impedanceanalysis, the reservoirs can be replaced with light guides, fibers orother optical devices to optically connect light sources, filters anddetectors to the fluidic sample.

FIGS. 12A-12E show a fluidic process that can be equivalent to theexemplary fluidic procedure for obtaining DNA as show in FIGS. 2A-2D andFIGS. 9A-9D. By way of example and not of limitation, FIG. 12B showswhen a fluid such as a lysate is flowed from a first reservoir 1007 to asecond reservoir 1008 through the channel arrangement 1005 containingthe functional element 1006 (e.g., DNA binding matrix), the DNA iscaptured in the functional element 1006. Then, FIG. 12E shows thestructure 1003 rotated such that the channel arrangement 1005 is nowaligned with reservoirs 1009, 1010 and the fluid can be flowed from athird reservoir 1009 to a fourth reservoir 1010. Such process can berepeated according to the number of steps desired to perform the fluidicoperation (e.g. DNA binding).

In some embodiments, a fluidic pressuring mechanism 1011 can beassociated with the reservoirs 1007-1010 to facilitate movement of thefluid. By way of example and not of limitation, the fluidic pressuringmechanism 1011 can be pistons, actuators, pumps, or valves. Pistons canhave various sizes and shapes, for example, to function with a syringe.Actuators can be internal to the reservoir or external to the reservoir.Pumps can also be internal or external to the reservoir, and can beelectrochemical pumps, parasitic pumps, electro-osmotic pumps or vacuumpumps. In some embodiments, a membrane can be used to press down in thereservoir, thus forcing the fluid to flow. The fluidic pressure obtainedfrom such fluidic pressuring mechanism can comprise positive or negativepressure. For example, the fluid can be pushed from the source of thefluid, or pulled from the destination of the fluid. However, thoseskilled in the art would understand that other types of pressuringmechanisms are possible to facilitate the movement of the fluid.

In some embodiments, the first reservoir 1007 can comprise elute buffer,while the second reservoir 1008 can comprise water. DNA can be elutedinto the water and mixing can be performed by pushing the fluidic samplethrough the functional element 1006 (e.g., membrane) in the channelarrangement 1005. A reservoir of the final stage can be, for example, amicrowell or a cartridge comprising a dry reagent, and the DNA can bedeposited. In some embodiments, the reservoir can comprise a PCR buffersuch that the PCR ready solution can be available without any dryreagents in a reaction structure. In some embodiments, the plurality ofreservoirs can comprise wash buffers to wash the functional element,channels, or structure a desired number of times.

In some embodiments, a reservoir can comprise a lysate. The fluidicdevice can be configured such that the lysate flows through thefunctional element of the channel to lyse the desired cells. By way ofexample, the functional element can be an orifice for lysing particularcells, which is known by those skilled in the art. Alternatively, anelectrical field can be applied to the channel. Another functionalelement can comprise a bead beating element to lyse desired cells.Consequently, a plurality of lysis operation can be performed and DNAcan be extract using a single fluidic device having various functionalelements.

FIG. 13 shows a close up view of the displaceable structure 1003 havinga channel arrangement 1005 with a functional element 1006. The exemplarydisplaceable structure 1003 is shown as a substantially disk shapedplanar shape. However, the displaceable structure can have other shapesand sizes, for example, substantially spherical. Additionally, thestructure 1003 can have a via 1012, as also shown in FIG. 14 with asecond structure 1013 layered on the first structure 1003 and adapted tooperate dependently or independently with the first structure 1003. Insome embodiments, when two structures 1003, 1013 are layered upon oneanother, the structures can be aligned such that the via 1012 of thefirst structure 1003 can be aligned with the channel arrangement 1014 ofthe second structure 1013. Therefore, a reservoir can be connected withthe via 1012 of the first structure 1003 and the fluid can flow throughthe channel arrangement 1014 of the second structure 1013, whilemaintaining minimal dead volume space. Vias facilitate the fluid to flowfrom one structure to another structure. Alternatively, tubing orintegrated pathways can be utilized (similar to wires or jumpers in aPCB) to fluidly connect two or more channels.

FIG. 15 shows a perspective view of an exemplary adapter 1001 with thedisplaceable structure 1003 associated with the adapter 1001. Thelocations of the ports 1002 a, 1002 b can be shown on the structure1003, with slots 1501, 1502 in the adapter 1001 such that reservoirs(e.g., syringes) can be connected with the structure 1003 through theports 1002 a, 1002 b.

FIG. 16 shows a close-up view of the displaceable structure 1003 withthe adapter 1001 and an exemplary reservoir 1007 such as a syringeconnected with the structure 1003. In some embodiments, the channelarrangement 1005 can be wide enough such that the fluid pressuringmechanism (e.g., a piston) can be configured to enter the channelarrangement 1005, thus requiring less pressure to move the fluid. Theproblem with the fluid material sticking to channel walls can beminimized since the piston can remove any material that may be stuck onthe channel walls. Conveniently, wider channels can be easier tofabricate. A functional element 1006 is also shown in the fluidic pathof the channel arrangement 1005.

FIG. 17 shows a schematic drawing of an alternative channel arrangementin the displaceable structure 1003 where there are two separate channelarrangements 1701, 1702 for two distinct fluidic flow paths.

FIGS. 18A-18D show an alternative device 1800 for performing fluidicoperations. In some embodiments, the slidably moveable structure 1801can be a square or a substantially rectangular rod between two fixedstructures 1807, 1808. The fixed structures 1807, 1808 can have portsfor flowing fluids from one port 1804 on one of the fixed structures1807 to a second port 1805 on the other fixed structure 1808, throughthe slidable moveable structure 1801. The slidable moveable structure1801 can have more than one distinct fluidic paths. For example, a firstfluidic path can be a substantially vertical fluidic path 1802, and asecond fluidic path can be a substantially inclined fluidic path 1803.The slanted fluidic path can be used to flow fluid from the first port1804 on one of the fixed structures 1807 to a second port 1806 on theother fixed structure 1808, thus fluidly connecting the two ports,wherein the two ports 1804, 1806 are not located directly across fromone another.

In some embodiments, the ports can be a luer connection to connect theports with, by way of example and not of limitation, syringes. In someembodiments, the ports can be a vertical hole to connect the ports with,by way of example and not of limitation, plungers. In some embodiments,the fixed structures 1807, 1808 can have guiding structures 1809 tofacilitate guiding and sliding of the slidable moveable structure 1801in alignment with the ports. The slidable moveable structure 1801 can bemade of materials such as TEFLON®, plastic with a low friction coating,or other hydrophobic coating material. Hydrophobic coating material canminimize the changes of the fluid leaking out of the fluidic device1800.

In some embodiments, the fixed structures 1807, 1808 can have slidingregions 1810 in which the slidable moveable rod 1801 can be configuredto slide against. Therefore, the slidable moveable rod 1801 makesminimal contact with the fixed structures, thus minimizing the surfacearea and friction between the slidable moveable rod 1801 and the fixedstructures.

In some embodiments, the slidable moveable rod 1801 can be larger thanthe vertical distance between the sliding regions thereby allowing theslidable moveable rod 1801 be compressed and fit snugly to create aseal. The slidable moveable rod 1801 can be adapted to expand in ahorizontal direction to accommodate such compression in the verticaldirection. Therefore, the guiding structures 1809 can be located on thefixed structures with consideration for expansion of the slidablemoveable rod 1801.

Various devices according to the embodiments of the present disclosurecan be used to perform plasma base pathogen detection (e.g., hepatitis).For example, a syringe containing blood can be connected with the luerconnection port. A filter can be placed in the hole 1803, 1802 of theslidable moveable rod 1803 to capture cells yet allow plasma to passthrough the filter. The lysate (e.g., blood) can be forced from thesyringe, through the filter to a reservoir or another syringe on theother side of the filter. Next, a DNA binding matrix can be placed inthe hole of the slidable moveable rod 1803 and the lysate can be forcedfrom one reservoir to another, through the DNA binding matrix. By way ofexample and not of limitation, the separated cells can be usedindependently for various applications such as detecting malaria or HIV.A capillary effect can also be used for sample collection such as forfinger pricks.

In some embodiments, can be desirable to have air in the fluidic devicesdescribed in various embodiments of the present disclosure. The air canbe used to dry the channels and/or the functional elements, or push outany remaining fluid in the channels.

In some embodiments, dielectrophoresis can be performed in addition tofiltering a sample concentration by way of evaporation. For example, achannel can be expanded and heated to control the flow of fluid from thechannels. The shape of the channel can also be optimized to form a filmof fluid in the channel to accelerate evaporation.

In some embodiments, the functional element can be a filteration elementconfigured to allow dead cell components to pass through the filter.Accordingly, cells larger than a selected side based on the filter willbe captured by the filter and smaller cell will pass through the filter.

In some embodiments, DNA extraction quality analysis can be performed byway of absorbance measurements. Thus, quality of the DNA can bedetermined before performing PCR reaction.

In some embodiments, a sample can be homogenized in the reservoir. Byway of example and not of limitation, a rotational grinder can beinstalled in a syringe to homogenize the sample. Then the fluidic samplecan be withdrawn or pulled by other reservoir (e.g., syringe) by pullingthe plunger of the other syringe, thus creating a vacuum. Alternatively,the reservoir comprising the grinder can also be configured to push outthe fluidic sample. Homogenization can be performed on samples such asfood, tissue, feces and/or soil.

In some embodiments, various samples can be mixed in the reservoirs. Forexample, a first reservoir can comprise a first sample. Then, the firstsample can be pushed to the second reservoir comprising a second sample.The second reservoir can comprise a 3D spiral shape to achieve thoroughmixing. In some embodiments, if the texture of the reservoir does notfacilitate ease of pushing out the sample, the sample can be pulled outby creating a vacuum as described previously.

In some embodiments, comprehensive tests can be performed using thefluidic device according to the present disclosure. Such test canmeasure protein concentration, bio markers, nucleic acids (bothpathogenic and genomic) and analytes using analysis methods known bythose skilled in the art. Cytometry can be performed to conduct cellbased analysis. By way of example and not of limitation, after cellfiltration, flow cytometry can be performed on one portion of the samplewhile the other undergoes sample preparation for ELISA, PCR, real-timePCR and/or qPCR. In some embodiments separate ELISA or ELISA with PCRtests can be performed by using the fluidic device according to thepresent disclosure, thus reducing health related problems.

In some embodiments, the fluidic device of the present disclosure can beused to separate blood serum, plasma and cells. Different filters can beimplemented as the functional element in the moveable structure toachieve desired separation and analysis. In some embodiments, thefunctional element can be a bubble removal element (e.g., de-bubbler).In some embodiments, impedance spectroscopy can be performed.

In some embodiments, droplet generation of the fluid (e.g., sample) canbe performed by precisely moving the moveable structure. By way ofexample and not of limitation, two reservoirs can perform droplets ofoil emulsion, which can then be used for digital PCR. An array can beintegrated into the system instead of cartridges to hold the droplets. Alow cost system can be made using the device described in U.S. PatentPublication No. 20100321696 published on Dec. 23, 2010 and U.S. PatentPublication No. 20110207137 published on Aug. 25, 2011, for qPCR fordigital PCR applications, both of which are incorporated by reference intheir entirety. Such system can be robust, low cost and portable.

Examples of samples that can be processed using the fluidic deviceaccording to the present disclosure can include, but not be limited toswabs, whole blood, food parts (homogenized), stool, urine, other bodilyfluids, soil, and/or forensic evidence.

In some embodiments, the fluidic device according to the presentdisclosure can be fabricated using plain plastic, polymer, and/or metalsheets and drawing holes in such material by drilling, laser cutting,using a water jet, EDM, etching and among other methods known by thoseskilled in the art. Injection molding methods can also be used. Otherfabrication methods such as laser fabrication, xerography, and othersemiconductor manufacturing processes. Low friction coatings andlubrication can be used to reduce friction of the moveable structure.

The examples set forth above are provided to give those of ordinaryskill in the art a complete disclosure and description of how to makeand use the embodiments of the present disclosure, and are not intendedto limit the scope of what the inventors regard as their disclosure.Modifications of the above-described modes for carrying out thedisclosure may be used by persons of skill in the art, and are intendedto be within the scope of the following claims. All patents andpublications mentioned in the specification may be indicative of thelevels of skill of those skilled in the art to which the disclosurepertains. All references cited in this disclosure are incorporated byreference to the same extent as if each reference had been incorporatedby reference in its entirety individually.

It is to be understood that the disclosure is not limited to particularmethods or systems, which can, of course, vary. It is also to beunderstood that the terminology used herein is for the purpose ofdescribing particular embodiments only, and is not intended to belimiting. As used in this specification and the appended claims, thesingular forms “a”, “an”, and “the” include plural referents unless thecontent clearly dictates otherwise. The term “plurality” includes two ormore referents unless the content clearly dictates otherwise. Unlessdefined otherwise, all technical and scientific terms used herein havethe same meaning as commonly understood by one of ordinary skill in theart to which the disclosure pertains.

A number of embodiments of the disclosure have been described.Nevertheless, it will be understood that various modifications may bemade without departing from the spirit and scope of the presentdisclosure. Accordingly, other embodiments are within the scope of thefollowing claims.

The invention claimed is:
 1. A device for performing fluidic operations,the device comprising: a fluidic chamber having a plurality of pairs ofports, a first port of each pair being located on a first side of thefluidic chamber and a second port of each pair being located on a secondside of the fluidic chamber, each second port being opposite arespective first port; a plurality of reservoirs adapted to be fluidlyconnected with the fluidic chamber at each of the plurality of pairs ofports, the plurality of reservoirs configured to flow fluid from a firstreservoir on the first side of the fluidic chamber through each of thefirst port and at least one of the second ports of the plurality ofpairs of ports to a second reservoir on the second side of the fluidicchamber, or vice versa, wherein each reservoir of the plurality ofreservoirs comprises a fluidic pressuring mechanism adapted tofacilitate a movement of the fluid between the first reservoir and thesecond reservoir through the fluidic chamber, and vice versa; and astructure slidably moveable within the fluidic chamber, the slidablymoveable structure comprising: one or more openings through thestructure and adapted to be aligned by a sliding of the structure withinthe fluidic chamber with at least one pair of the plurality of pairs ofports to allow fluidic connection between one or more reservoirs on thefirst side and respective one or more reservoirs on the second side, theone or more openings being moveably alignable with a desired pair ofports by the sliding of the structure to allow the movement of the fluidbetween the first reservoir, via the one or more openings thereinthrough the slidably moveable structure, and the second reservoir, andvice versa; and at least one interaction element disposed within atleast one of the openings and operable for interacting with the fluidtherein, the at least one interaction element comprising a functionalelement, which is located in a flow path of the fluid through the atleast one of the openings when the fluid flows through the fluidicchamber, the functional element comprising one or more of a DNA bindingmatrix or a lysis structure.
 2. The device according to claim 1, whereinthe functional element, which is located in a flow path of the fluidthrough the at least one of the openings when the fluid flows throughthe fluidic chamber, further comprises a filtering component.
 3. Thedevice according to claim 2, wherein movement of the functional elementthrough sliding of the slidably moveable structure is synchronous withmovement of the opening comprising the functional element.
 4. The deviceaccording to claim 1, wherein the structure is slidably moveable in anaxial direction of the device.
 5. The device according to claim 1,wherein the structure is slidably moveable in a radial direction of thedevice.
 6. The device according to claim 1, wherein the fluidicpressuring mechanism is adapted to facilitate the movement of the fluidby one or more of a positive pressure or a negative pressure.
 7. Thedevice according to claim 1, wherein the pressuring mechanism isselected from the group consisting of: a piston, an internal actuator,an external actuator, and a pump.
 8. The device according to claim 1,wherein the reservoirs are selected from the group consisting of:syringes, syringes with pistons, tubes with a pinching mechanism,pouches, planar reservoirs and channels, reservoirs with flexiblemembranes, pipettes, and cartridges.
 9. The device according to claim 2,wherein the filtering component is selected from the group consistingof: a plasma filter, a cell filter, a mixing filter, and a bindingfilter.
 10. A device for performing fluidic operations, the devicecomprising: a first fixed structure and a second fixed structure, eachhaving a plurality of ports; a plurality of reservoirs adapted to befluidly connected with the plurality of ports, the plurality ofreservoirs configured to flow fluid from a first reservoir associatedwith the port on the first fixed structure, and connected to the port onthe first fixed structure on a first side thereof, to a second reservoirassociated with the port on the second fixed structure, and connected tothe port on the second fixed structure on a side thereof opposite fromthe first reservoir, wherein each reservoir of the plurality ofreservoirs comprises a fluidic pressuring mechanism adapted tofacilitate a movement of the fluid between the first reservoir and thesecond reservoir, or vice versa, the pressuring mechanism comprising oneor more of a piston, an internal actuator, an external actuator or apump; and a structure slidably moveable between the first fixedstructure and the second fixed structure, the slidably moveablestructure comprising: one or more openings through the structure andadapted to be aligned by a sliding of the structure with at least oneport of the first fixed structure and at least one port of the secondfixed structure to allow fluidic connection between one or morereservoirs associated with the first fixed structure, via the one ormore openings therein through the slidably moveable structure, andrespective one or more reservoirs associated with the second fixedstructure, and vice versa; and at least one interaction element disposedwithin at least one of the one or more openings and operable forinteracting with the fluid therein.
 11. The device according to claim10, wherein the one or more openings of the structure are substantiallyvertically or inclinedly located within the structure.
 12. The deviceaccording to claim 10, further comprising a plurality of sliding regionsconnected to the first fixed structure between the first fixed structureand the plurality of ports on the first fixed structure, and connectedto the second fixed structure between the second fixed structure and theplurality of ports on the second fixed structure.
 13. The deviceaccording to claim 10, wherein the plurality of ports comprises a Luerconnection.
 14. A method of performing fluidic operations using thedevice, which is described according to claim 1, the method comprising:a) slidably moving the structure to align the at least one opening witha first pair of ports; b) transferring the fluid from the reservoir onthe first side of the fluidic chamber to the reservoir on the secondside of the fluidic chamber by flowing the fluid through the functionalelement in the opening; and c) repeating a)-b) a desired number oftimes.
 15. The method according to claim 14, wherein the fluidicoperation is extracting DNA.
 16. The method according to claim 14,wherein the fluidic operation is lysating.
 17. The method according toclaim 14, wherein the fluidic operation is elution.
 18. A device forperforming fluidic operations, the device comprising: a fluidic chamberhaving a plurality of pairs of ports, a first port of each pair beinglocated on a first side of the fluidic chamber and a second port of eachpair being located on a second side of the fluidic chamber, each secondport being opposite a respective first port; a plurality of reservoirsadapted to be fluidly connected with the fluidic chamber at each of theplurality of pairs of ports, the plurality of reservoirs configured toflow fluid from a first reservoir on the first side of the fluidicchamber through each of the first port and at least one of the secondports of the plurality of pairs of ports to a second reservoir on thesecond side of the fluidic chamber, or vice versa, wherein eachreservoir of the plurality of reservoirs comprises a fluidic pressuringmechanism adapted to facilitate a movement of the fluid between thefirst reservoir and the second reservoir through the fluidic chamber,and vice versa, the pressuring mechanism comprising one or more of apiston, an internal actuator, an external actuator or a pump; and astructure slidably moveable within the fluidic chamber, the slidablymoveable structure comprising: one or more openings through thestructure and adapted to be aligned by a sliding of the structure withinthe fluidic chamber with at least one pair of the plurality of pairs ofports to allow fluidic connection between one or more reservoirs on thefirst side and respective one or more reservoirs on the second side, theone or more openings being moveably alignable with a desired pair ofports by the sliding of the structure to allow the movement of the fluidbetween the first reservoir, via the one or more openings thereinthrough the slidably moveable structure, and the second reservoir, andvice versa; and at least one interaction element disposed within atleast one of the openings and operable for interacting with the fluidtherein.
 19. A device for performing fluidic operations, the devicecomprising: a first fixed structure and a second fixed structure, eachhaving a plurality of ports; a plurality of reservoirs adapted to befluidly connected with the plurality of ports, the plurality ofreservoirs configured to flow fluid from a first reservoir associatedwith the port on the first fixed structure, and connected to the port onthe first fixed structure on a first side thereof, to a second reservoirassociated with the port on the second fixed structure, and connected tothe port on the second fixed structure on a side thereof opposite fromthe first reservoir, wherein each reservoir of the plurality ofreservoirs comprises a fluidic pressuring mechanism adapted tofacilitate a movement of the fluid between the first reservoir and thesecond reservoir, or vice versa; and a structure slidably moveablebetween the first fixed structure and the second fixed structure, theslidably moveable structure comprising: one or more openings through thestructure and adapted to be aligned by a sliding of the structure withat least one port of the first fixed structure and at least one port ofthe second fixed structure to allow fluidic connection between one ormore reservoirs associated with the first fixed structure, via the oneor more openings therein through the slidably moveable structure, andrespective one or more reservoirs associated with the second fixedstructure, and vice versa; and at least one interaction element disposedwithin at least one of the one or more openings and operable forinteracting with the fluid therein, the at least one interaction elementcomprising a functional element, which is located in a flow path of thefluid through the at least one of the openings when the fluid flowsthrough the fluidic chamber, the functional element comprising one ormore of a DNA binding matrix or a lysis structure.